1. Field of the Invention
The present invention pertains to biocompatible, antithrombogenic materials, and more particularly relates to substances that impart antithrombogenic qualities to a biomedical polymer structure or polymer coating.
2. Description of the Prior Art
An increasing amount of medical hardware is being developed that requires certain components or surfaces thereof to come into contact with a patient's blood flow. It is essential that such blood contacting surfaces be as compatible with the blood as possible which requires that measures be taken to prevent or at least minimize the coagulation of blood. Probes, sensors, catheter devices, prostheses and implantable devices all stand to benefit from such enhanced hemocompatibility as excessive coagulation can impair sensitivity and function, can reduce flow and cause further problems downstream.
A number of different approaches have been employed in the past in an effort to address this problem. Certain drugs introduced into the recirculating blood supply have been found to be effective in decreasing or delaying coagulation by targeting and interfering in any one or more of the many complex interrelationships and sub-processes involved in the coagulation process. Heparin is a compound well-known for its ability to prevent clotting and is in fact normally present in blood in small concentrations. By introducing additional heparin into the blood supply, coagulation rates are reduced.
Such approach does however have the inherent disadvantage that relatively high doses of pharmaceutical agents are caused to circulate throughout the entire circulatory system while their effect is required at only a relatively small, localized site. Substantially undesirable side effects may be associated with such drugs and it may be desirable for the blood to retain its ability to coagulate in other parts of the body. This problem has been addressed with some success by incorporating in or applying to the blood contacting surface a substance that releases an anticoagulant for an extended period of time. The anticoagulant concentration is therefore relatively high at precisely the point its effect is most needed while its overall concentration throughout the body remains relatively low if not negligible. Heparin-benzalkonium chloride complex (HBAC) and heparin-tridodecylmethylammonium chloride complex (H-TDMAC) have been found relatively effective as anticoagulant releasing agents although each has associated disadvantages. HBAC forms a rather brittle film and releases heparin very slowly. HTDMAC is more flexible but releases heparin at an even slower rate. Antithrombogenic activity decreases as a function of time and eventually completely ceases upon total depletion of the heparin.
Efforts have alternatively been directed towards developing a material which the blood does not recognize as foreign. Failure to properly recognize a foreign substance prevents the triggering of the coagulation process, i.e. proteins are not deposited on such foreign substance, red blood cells are not destroyed nor become adhered thereto, while platelet aggregation and adhesion also fails to take place. This has been achieved to a limited degree by selecting or synthesizing substances that mimic critical surface characteristics of cell membranes. Cell membranes generally comprise an asymmetrical lipid matrix of polar lipids in which certain specific functional groups are arranged on the outer surface. Synthetic polymer formulations that incorporate similar lipids having similar functional groups have been found to exhibit some antithrombogenic characteristics. Phosphatidylcholine has been found to impart some antithrombogenicity to materials in which it is incorporated.
Although both of the above described approaches do provide some antithrombogenic effects, each is plagued with substantial inherent limitations. Moreover, far greater antithrombogenicity than is currently available is needed, or would be desirable in many biomedical applications.